rs10947262

Variant names:

• chr6-32405535-C-T
• rs10947262
• NM_001304561.2:c.80-249G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304561.2(BTNL2):​c.80-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 535,802 control chromosomes in the GnomAD database, including 5,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1361 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4086 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• Publications: 65 publications found

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.80-249G>A		intron	N/A	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.384C>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.80-249G>A		intron	N/A	ENSP00000390613.3	Q9UIR0-7
	BTNL2	ENST00000446536.3	TSL:1	c.80-252G>A		intron	N/A	ENSP00000388434.2	F6UPS5
	BTNL2	ENST00000465865.6	TSL:1	n.80-249G>A		intron	N/A	ENSP00000420063.1	F8WDK6

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18558 AN: 152054 Hom.: 1358 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.122 AC: 46660 AN: 383630 Hom.: 4086 Cov.: 2 AF XY: 0.123 AC XY: 25416 AN XY: 206256

African (AFR) AF: 0.132 AC: 1497 AN: 11302

American (AMR) AF: 0.175 AC: 3730 AN: 21272

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 1072 AN: 12622

East Asian (EAS) AF: 0.354 AC: 7922 AN: 22386

South Asian (SAS) AF: 0.166 AC: 7986 AN: 48152

European-Finnish (FIN) AF: 0.168 AC: 3476 AN: 20638

Middle Eastern (MID) AF: 0.114 AC: 193 AN: 1696

European-Non Finnish (NFE) AF: 0.0817 AC: 18310 AN: 224030

Other (OTH) AF: 0.115 AC: 2474 AN: 21532

GnomAD4 genome AF: 0.122 AC: 18571 AN: 152172 Hom.: 1361 Cov.: 32 AF XY: 0.128 AC XY: 9548 AN XY: 74398

African (AFR) AF: 0.140 AC: 5799 AN: 41496

American (AMR) AF: 0.143 AC: 2191 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1597 AN: 5186

South Asian (SAS) AF: 0.194 AC: 933 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1882 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5552 AN: 68002

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.0965 Hom.: 3721

Bravo AF: 0.118

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.67
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10947262; hg19: chr6-32373312;